Abstract
We used time-of-flight secondary ion mass spectrometry (ToF-SIMS) to study changes in the composition of the plasma membranes of human fetal fibroblasts under the action of nanosized anions of silicon molybdic acid. The dependences of the mass spectra of the main lipids of the plasma membranes on the silicon molybdate concentration were measured and interpreted; the dependences correlate with the layer-by-layer distributions and with the affinity of cholesterol for phospholipids. A new effect for cell biochemistry was discovered, that is, a significant decrease in the relative concentrations of cholesterol and sphingomyelin in plasma membranes under the effect of multiply charged heteropoly anions (HPAs). In aqueous silicon molybdate solutions with a concentration of c ≈ 10 µM/L and an exposure time of 48 h, the amount of cholesterol in plasma membranes decreased by 2–2.5 times, while the amount of sphingomyelin decreased by 20–25%. A new mechanism is proposed for the initial effect of HPA on plasma membranes, which consists of selective etching by multiply charged anions. According to the proposed mechanism, cholesterol and sphingomyelin, the main regulators of permeability and microviscosity of plasma membranes, are extracted from the plasma membrane at the first stage of the interaction of the polyoxometallate anion with the cell. As a consequence of the increased permeability of the plasma membranes in cells, acceleration of vital transmembrane and lateral processes may occur.
Similar content being viewed by others
Notes
The well-known values of the affinity of SM and PC for cholesterol, δ, are in magnitude in the same sequence as the scale of the initial decrease of the corresponding peaks in the mass spectra: δ (SM) > δ (PC) [42]. It is natural to assume that in some cases, cholesterol molecules leave the plasma membrane simultaneously with the bipolar head parts of phospholipids (SM, PC, PS, and PE). The similarity of the concentration dependences of the peaks of cholesterol (m/z 369) and SM (m/z 265) (Fig. 3) confirms this assumption.
REFERENCES
G. I. T. Cooper, P. I. Kitson, R. Winter, et al., “Modular redox-active inorganic chemical cells: iCHELLs,” Angew. Chem., Int. Ed. 50, 10373 (2011). https://doi.org/10.1002/anie.201105068
I. K. Song, I. E. Lyons, and M. A. Barteau, “Correlation of alkane oxidation performance with STM and tunneling spectroscopy measurements of heteropolyacid catalysts,” Catal. Today 81, 137 (2003). https://doi.org/10.1016/S0920-5861(03)00107-X
M. T. Pope, “Polyoxometalates,” in Encyclopedia of Inorganic and Bioinorganic Chemistry, 1st ed., Ed. by S. R. A. Somerset (Wiley, NJ, 2011).
J. T. Rhule, C. L. Hill, D. A. Judd, et al., “Polyoxometalates in medicine,” Chem. Rev. 98, 327 (1998). https://doi.org/10.1021/cr960396q
B. Hasenknopf, “Polyoxometalates: Introduction to a class of inorganic compounds and their biomedical applications,” Front. Biosci. 10, 275 (2005). https://doi.org/10.2741/1527
A. Bijelic, M. Aureliano, and A. Rompel, “The antibacterial activity of polyoxometalates: structures, antibiotic effects and future perspectives,” Chem. Commun. 54, 1143 (2018). https://doi.org/10.1039/C7CC07549A
X. Wang, J. Wang, W. Zhang, et al., “Inhibition of human immunodeficiency virus type 1 entry by a Keggin polyoxometalate,” Viruses 10, 265 (2018). https://doi.org/10.3390/v10050265
N. Gao, H. Sun, K. Dong, et al., “Transition-metal-substituted polyoxometalate derivatives as functional antiamyloid agents for Alzheimer’s disease,” Nat. Commun. 5, 3422 (2014). https://doi.org/10.1155/2015/753751
Y. Qi, Y. Xiang, J. Wang, et al., “Inhibition of hepatitis C virus infection by polyoxometalates,” Antiviral Res. 100, 392 (2013). https://doi.org/10.2217/fvl.14.89
W. Qi, Y. Qin, Y. Qi, et al., “In vitro antitumor activity of a Keggin vanadium-substituted polyoxomolybdate and its ctDNA binding properties,” J. Chem. 2015, 753751 (2014). https://doi.org/10.1155/2015/753751
L. Wang, K. Yu, J. Zhu, et al., “Inhibitory effects of different substituted transition metal-based Krebs-type sandwich structures on human hepatocellular carcinoma cells,” Dalton Trans. 46, 2874 (2017). https://doi.org/10.1039/C6DT02420C
G. Geisberger, E. B. Gyenge, C. Maake, et al., “Trimethyl and carboxymethyl chitosan carriers for bio-active polymer-inorganic nanocomposites,” Carbohydr. Res. 91, 58 (2013). https://doi.org/10.1016/j.carbpol.2012.08.009
S. Dianat, A. K. Bordbar, S. Tangestaninejad, et al., “In vitro antitumor activity of parent and nano-encapsulated mono cobalt-substituted Keggin polyoxotungstate and its ctDNA binding properties,” Chem.-Biol. Interact. 215, 25 (2014). https://doi.org/10.1016/j.cbi.2014.02.011
S. Dianat, A. K. Bordbar, S. Tangestaninejad, et al., “CtDNA interaction of co-containing keggin polyoxomolybdate and in vitro antitumor activity of free and its nano-encapsulated derivatives,” J. Iran. Chem. Soc. 13, 1895 (2016). https://doi.org/10.1007/s13738-016-0906-y
A. Bijelic, M. Aureliano, and A. Rompel, “Polyoxometalates as potential next-generation metallodrugs in the combat against cancer,” Angew. Chem., Int. Ed. Engl. 58, 2980 (2019). https://doi.org/10.1002/anie.201803868
N. I. Gumerova, E. Al-Sayed, L. Krivosudsky, et al., “Antibacterial activity of polyoxometalates against moraxella catarrhalis,” Front. Chem. 6, 336 (2018). https://doi.org/10.3389/fchem.2018.00336
O. A. Lopatina, I. A. Suetina, M. V. Mezentseva, L. I. Russu, S. A. Kovalevskiy, E. M. Balashov, S. A. Ulasevich, A. I. Kulak, D. A. Kulemin, N. M. Ivashkevich, and F. I. Dalidchik, “Effects of anion charge on the biological activity of Keggin heteropoly acids,” Russ. J. Phys. Chem. B 14, 81 (2020).
H. Nabika, Y. Inomata, E. Itoh, and K. Unoura, “Activity of Keggin and Dawson polyoxometalates toward model cell membrane,” RSC Adv. 3, 21271 (2013). https://doi.org/10.1039/C3RA41522H
H. Nabika, A. Sakamoto, R. Tero, et al., “Imaging characterization of cluster-induced morphological changes of a model cell membrane,” J. Phys. Chem. C 120, 15640 (2016). https://doi.org/10.1021/acs.jpcc.5b08014
B. Jing, M. Hutin, E. Connor, et al., “Polyoxometalate macroion induced phase and morphology instability of lipid membrane,” Chem. Sci. 4, 3818 (2013). https://doi.org/10.1039/C3SC51404H
D. Kobayashi, Y. Ouchi, M. Sadakane, et al., “Structural dependence of the effects of polyoxometalates on liposome collapse activity,” Chem. Lett. 46, 533 (2017). https://doi.org/10.1246/cl.161172
D. Kobayashi, H. Nakahara, O. Shibata, et al., “Interplay of hydrophobic and electrostatic interactions between polyoxometalates and lipid molecules,” J. Phys. Chem. C 121, 12895 (2017). https://doi.org/10.1021/acs.jpcc.7b01774
V. G. Ivkov and G. N. Berestovskii, Biological Membrane Lipid Bilayer (Nauka, Moscow, 1982) [in Russian].
K. Chughtai and R. M. Heeren, “Mass spectrometry imaging for biomedical tissue analysis,” Chem. Rev. 110, 3237 (2010). https://doi.org/10.1021/cr100012c
X. Hua, M. J. Marshall, Y. Xiong, et al., “Two-dimensional and three-dimensional dynamic imaging of live biofilms in a microchannel by time-of-flight secondary ion mass spectrometry,” Biomicrofluidics 9, 031101 (2015). https://doi.org/10.1039/c3ay26513g
C. Bich, D. Touboul, and A. Brunelle, “Cluster TOF-SIMS imaging as a tool for micrometric histology of lipids in tissue,” Mass Spectrosc. Rev. 33, 442 (2014). https://doi.org/10.1002/mas.21399
N. Winograd, “Gas cluster ion beams for secondary ion mass spectrometry,” Ann. Rev. Anal. Chem. 11, 29 (2018). https://doi.org/10.1146/annurev-anchem-061516-045249
M. K. Passarelli and N. Winograd, “Lipid imaging with time-of-flight secondary ion mass spectrometry (ToF-SIMS),” Biochim. Biophys. Acta 1811, 976 (2011). https://doi.org/10.1016/j.bbalip.2011.05.007
Q. P. Vanbellingen, A. Castellanos, M. Rodriguez-Silva, et al., “Analysis of chemotherapeutic drug delivery at the single cell level using 3D-MSI-TîF-SIMS,” J. Am. Soc. Mass Spectrom. 27, 2033 (2016). https://doi.org/10.1007/s13361-016-1485-y
H. Jungnickel, P. Laux, and A. Luch, “Time-of-flight secondary ion mass spectrometry (ToF-SIMS): A new tool for the analysis of toxicological effects on single cell level,” Toxics 4, 5 (2016). https://doi.org/10.3390/toxics4010005
N. Winograd, “Imaging mass spectrometry on the nanoscale with cluster ion beams,” Anal. Chem. 87, 328 (2015). https://doi.org/10.1021/ac503650p
A. G. Pogopelov, A. A. Gulin, V. N. Pogopelova, A. I. Panait, M. A. Pogorelova and V. A. Nadtochenko, “The use of ToF-SIMS for analysis of bioorganic samples,” Biophysics 63, 215 (2018).
M. S. Wagner and D. G. Castner, “Characterization of adsorbed protein films by time-of-flight secondary ion mass spectrometry with principal component analysis,” Langmuir 17, 4649 (2001). https://doi.org/10.1021/la001209t
A. G. Sostarecz, C. M. McQuaw, A. G. Ewing, and N. Winograd, “Phosphatidylethanolamine-induced cholesterol domains chemically identified with mass spectrometric imaging,” J. Am. Chem. Soc. 126, 13882 (2004). https://doi.org/10.1021/ja0472127
M. Urbini, V. Petito, F. de Notaristefani, et al., “ToF-SIMS and principal component analysis of lipids and amino acids from inflamed and dysplastic human colonic mucosa,” Anal. Bioanal. Chem. 409, 6097 (2017). https://doi.org/10.1007/s00216-017-0546-9
R. Bro and A. K. Smilde, “Principal component analysis,” Anal. Methods 6, 2812 (2014). https://doi.org/10.1039/C3AY41907J
S. A. Kovalevskii, O. A. Lopatina, F. I. Dalidchik, O. V. Baklanova, I. A. Suetina, L. I. Russu, E. A. Gushchina, E. I. Isaeva, and M. V. Mezentseva, “Effect of Keggin heteropoly acids on human embryo fibroblast cells,” Nanotechnol. Russ. 13, 400 (2018).
I. A. Suetina, M. V. Mezentseva, E. A. Gushchina, et al., “Study of the growth activity and viability of cultured human embryo fibroblasts under the influence of polyoxametallates,” Inform. Byull. Kletoch. Kul’t. 31, 67 (2015).
F. Draude, M. Korsgen, A. Pelster, et al., “Characterization of freeze-fractured epithelial plasma membranes on nanometer scale with ToF-SIMS,” Anal. Bioanal. Chem. 407, 2203 (2014). .https://doi.org/10.1007/s00216-014-8334-2
L. D. Bergel’son, Membranes, Molecules, Cells (Nauka, Moscow, 1982) [in Russian].
R. Bittman and S. Rottem, “Distribution of cholesterol between the outer and inner halves of the lipid bilayer of mycoplasma cell membranes,” Biochem. Biophys. Res. Commun. 71, 318 (1976). https://doi.org/10.1016/0006-291x(76)90285-0
L. I. Ivanova, “The effect of cholesterol on the plasma membranes of tumor and normal cells,” Cand. Sci. (Biol.) Dissertation (Moscow, 1984), p. 114.
V. G. Ivkov and G. N. Berestovskii, Biological Membrane Lipid Bilayer (Nauka, Moscow, 1982) [in Russian].
J. Cui, X. Fu, J. Xie, et al., “Critical role of cellular cholesterol in bovine rotavirus infection,” Virology J. 11, 98 (2014). https://doi.org/10.1186/1743-422X-11-98
Funding
This work was carried out as part of a state assignment on the topic “Fundamentals of creating a new generation of nanostructured systems with unique operational electrical and magnetic properties” (project no. 0082-2018-0003, registration no. AAAA-A18-118012390045-2) and supported by the Russian Foundation for Basic Research (project no. 18-54-00004 Bel_a) and the Belarusian Foundation for Basic Research (agreement no. Kh18R-110).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Translated by O. Zhukova
Rights and permissions
About this article
Cite this article
Kovalevskiy, S.A., Gulin, A.A., Lopatina, O.A. et al. The Effect of Nanosized Silicon Molybdate Anions on the Plasma Membrane of Human Fetal Fibroblasts. Nanotechnol Russia 14, 481–488 (2019). https://doi.org/10.1134/S1995078019050082
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1995078019050082